The aim of the proposed research is to improve the understanding and treatment of human anxiety. Pilot research has suggested that similar nonhuman primate behaviors are elicited by dangerous situations, by electrical stimulation of the locus coeruleus (LC) noradrenergic system, or by chemical agents which activate the LC. These behaviors were blocked by agents which diminish the activity of the locus coeruleus on its efferent projections. Agents studied with this effect included several drugs with anxiolytic action in humans. In the opposite direction, chemical agents which increase LC activity increased the same behaviors and have been reported to induce anxiety in humans. We hypothesize on the basis of these and other data that alterations in LC activity are relevant to human anxiety and to the mode of action of anxiolytic drugs. Our objective is to confirm these pilot observations in further studies of behaviors in monkeys. We have these specific hypotheses to test: (1) that identical behaviors in monkeys are produced by any procedure which increases LC activity; (2) that these behaviors are reduced by any procedure which reduces the effects of LC activity on its projection areas; (3) that the same behaviors are produced by natural threats or classically conditioned by signals warning of impending noxious or aversive electrical shocks; (4) that lesions of the locus coeruleus shows specific activation in the presence of threats or conditioned shocks; and (6) that the effects of LC stimulation in monkeys free to interact socially are opposite to the effects of LC lesions in free moving monkeys. The methods will include the use of pharmacologic agents with specific effects on LC activity, agents with known human anxiolytic activity, electrical stimulation and lesions of the locus coeruleus, and single unit activity from the LC in awake monkeys.